Preterm delivery (PTD) is defined as the delivery of a fetus after 20 weeks and before 37 completed weeks of gestation. Although the rate of pre term delivery varies from 7-10% worldwide, it is the single largest contributor to perinatal mortality in the developed world. North American studies confirm that infants born before 32 weeks gestation account for approximately 70% of infant mortality rates. It follows that if the number of preterm births were to decrease so would the perinatal mortality rate. However, despite extensive research in this area, the preterm delivery rate has remained stagnant. In the USA, it has even increased from 7-10% in 1990s to a record high of 12.9% in 2007.
Risk factors for early delivery include: infection, poor nutritional status, extremes of reproductive age, trauma, substance abuse and short interval between pregnancies. However, even when these risk factors are avoided, preterm delivery may occur. The single most significant risk for preterm delivery is a prior preterm birth. Preterm Delivery is usually preceded by preterm labor (PTL). Much research has been performed concerning the aetiology of preterm labor, but the exact cause remains unclear.
Clinical therapeutic approaches designed to prevent preterm labor are very limited. In 1998, maternal plasma fetal DNA was shown to be a marker for preterm labor (Leung T et al (1998) Lancet 352, 1904-1905). Although DNA is known to be a potent activator of the innate immune system, such activation is typically observed from microbial DNA, that is, DNA which is derived from a bacterial or viral source.
Toll-like Receptors (TLRs) form a family of pattern recognition receptors which have a key role in activating the innate immune response. Eleven Toll-like Receptors have been identified in humans to date. The members of the Toll-like Receptor family are highly conserved, with most mammalian species having between 10 to 15 Toll-like Receptors. Each Toll-like Receptor recognises specific pathogen-associated molecular signatures. Toll-like Receptor 9 (TLR9, TLR-9) senses CpG motifs in DNA. These are more common in bacterial and viral DNA and TLR9 has been shown to have an important role in the sensing of various pathogens during host defence.
The onset of preterm labor is typically treated using tocolytic therapies involving beta2 adrenergic receptor agonists. However, the administration of such beta2 adrenergic receptor agonists can lead to the occurrence of undesirable side effects, such as heart palpitations. There is therefore a need for improved therapeutic treatments for preterm labor.